High triglycerides nearly halve the HDL-raising benefit of a protective CETP promoter variant, large PREVEND study finds (J Clin Endocrinol Metab 2005)

Original title: The effect of cholesteryl ester transfer protein -629C->A promoter polymorphism on high-density lipoprotein cholesterol is dependent on serum triglycerides

J Clin Endocrinol Metab · 19 April 2005 · 6

Borggreve SE, Hillege HL, Wolffenbuttel BH, de Jong PE, Bakker SJ, van der Steege G, van Tol A, Dullaart RP, PREVEND Study Group

Since CETP-mediated cholesteryl ester transfer out of HDL is stimulated by high triglycerides, this study tested whether triglycerides modify the effect of the CETP -629C>A promoter polymorphism on HDL-cholesterol (HDL-C) in 7083 nondiabetic subjects from the PREVEND population, with serum apolipoprotein A-I available in 6948. HDL-C and apoA-I were higher in -629AA (22.9%) than -629CC (26.8%) homozygotes (both P less than 0.001), an effect averaging 0.15 mmol/L in the lowest triglyceride tertile but only 0.08 mmol/L in the highest tertile (P less than 0.01). Multiple regression confirmed HDL-C was determined by CETP promoter genotype, gender, triglycerides, and interactions between triglycerides and genotype (P less than 0.05), independent of waist, insulin resistance, alcohol, age, and lipid-lowering drugs. The TaqIB polymorphism showed a similar triglyceride interaction, but the -629C>A polymorphism did not interact with obesity or insulin resistance. The authors conclude high triglycerides diminish the HDL-C-raising effect of the CETP -629A allele.

Original abstract

Context: The -629C-->A cholesteryl ester transfer protein (CETP) promoter polymorphism is a determinant of HDL cholesterol (HDL-C). The effect of the closely linked CETP TaqIB polymorphism on HDL-C has been suggested to be modified by obesity and hyperinsulinemia.

Objective: Because the CETP-mediated cholesteryl ester transfer out of HDL is stimulated by high triglycerides, we hypothesized that triglycerides modify the effect of the CETP -629C-->A promoter polymorphism on HDL-C.

Design: In 7083 nondiabetic subjects of the PREVEND population, the -629C-->A promoter polymorphism, HDL-C, serum triglycerides, waist circumference, and insulin resistance (HOMA(ir)) were determined. Serum apolipoprotein A-I was available in 6948 subjects. The TaqIB polymorphism was also assessed.

Setting: The study is set in the general community.

Results: HDL-C and serum apolipoprotein A-I were on average 0.14 mmol/liter and 0.05 g/liter higher in -629AA (22.9%) compared to -629CC (26.8%) homozygotes (P < 0.001 for both). This genotype effect on HDL-C was on average 0.15 mmol/liter in the lowest triglyceride tertile but only 0.08 mmol/liter in the highest tertile (P < 0.01). Multiple regression analysis showed that HDL-C was determined by the CETP promoter variant (P < 0.001), gender (P < 0.001), triglycerides (P < 0.001), and interactions between triglycerides and genotype (P < 0.05), between triglycerides and gender (P < 0.05), and between genotype and gender (P < 0.05), independently from waist, HOMA(ir), alcohol use, age, and use of lipid-lowering drugs. The TaqIB polymorphism also interacted with triglycerides on HDL-C. The -629C-->A promoter polymorphism did not interact with obesity and HOMA(ir) on HDL-C.

Conclusions: The HDL-C-raising effect of the CETP -629A allele is diminished with higher triglycerides, which may be explained by a predominant effect of triglyceride-rich lipoproteins over circulating CETP itself on cholesteryl ester transfer out of HDL with rising triglycerides.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.